Table 1.
Summary of the major findings regarding Orai and STIM functional effects in melanocytes and melanoma
| Effects of | Signalling | ||||||
|---|---|---|---|---|---|---|---|
| CRAC | Effects of | Orai–STIM on | pathways/ | ||||
| components | Orai–STIM on | migration and | proteins | Other functional | |||
| Cells examined | identified | SOCE/I CRAC | proliferation | invasion | involved | effects | |
| Feldman et al. 2010 | Malignant and non‐malignant B16BL6 mouse cells | Orai1 and STIM1 | SOCE is detectable and is higher in the malignant cells | ND | ND | PKB/AKT | Inhibition of mitochondrial Ca2+ buffering sensitizes melanoma cells to apoptosis |
| Stanisz et al. 2012 | Primary human melanocytes | Orai1–3, STIM1–2(Orai1 and STIM2 highest expression) | SOCE and I CRAC are detectable | Promote | ND | ND | Orai1 and STIM2 promote melanin synthesis |
| Stanisz et al. 2014 | Human melanoma | Orai1–3, STIM1–2 (Orai1 and STIM2 highest expression) | SOCE is detectable (no differences between melanocytes and different melanoma cell lines) | Suppress | Promote | MITFJARID1BBrn2 | Orai1 and STIM2 are highly expressed in invasive tumour fronts in human melanoma patient samples |
| Umemura et al. 2014 | Human melanoma | Orai1, STIM1 (other Orai isoforms and STIM2 not detected) | SOCE is increased in invasive melanoma cell lines vs. primary melanoma cells and melanocytes | Promote (minor effect) | Promote | ERK | Orai1‐ and STIM1‐silencing resulted in fewer lung metastases |
| Melanocyte cell line | Low Orai1 expression | ||||||
| Sun et al. 2014 | Human melanoma | Orai1, STIM1 | SOCE is detectable10% FCS induces Ca2+ oscillations while Tg sustained Ca2+ entry | No effect | Promote (oscillatory SOCE)Suppress (sustained SOCE) | Src | Promotion of plasma membrane localization of MT1‐MMP and invadopodium maturation |
| Hooper et al. 2015 | Human melanoma | Orai1‐3, STIM1‐2 (Orai2, ‐3 higher expression than Orai1; STIM1 higher expression than STIM2) | SOCE and I CRAC are detectable but are much lower in highly invasive melanoma cells | ND | Suppress | Wnt5a, PKC | Wnt5a regulates SOCE amplitude and melanoma invasiveness |
ND, not determined. MT1‐MMP, membrane type 1 metalloprotease; Src, proto‐oncogene tyrosine‐protein kinase.